Investigating inflammatory processes of plaque destabilization using proteomics

SSAR 2022

Lasse Lorentzen

Extracellular matrix remodeling in atherosclerosis

Extracellular matrix remodeling in atherosclerosis



  • Synthesis of new extracellular matrix (ECM) proteins
  • Degradation of “old” ECM proteins
  • Remodeling of the vascular ECM takes place under atherosclerotic conditions
  • Hypothesis: Remodeling of the vascular ECM is a key driver in plaque destabilization

Proteomics investigation of ECM remodelling

Proteomics workflow

Study design

  • 21 symptomatic plaques from the carotid artery
    • 7 Hard, 7 Mixed, 7 Soft plaques
  • Compared by proteomics

Differentially regulated proteins

Over-representation analysis

N-terminomics investigation of protelytic ECM remodelling

ECM degradation by proteolytic enzymes

ECM degradation by proteolytic enzymes

ECM degradation by proteolytic enzymes

Proteomics workflow

Differentially regulated free N-termini

Most regulated free N-termini are non-canonical

Degradation of Collagen type VI

Degradation of other Collagens

Degradation of Fibronectin

Degradation of other basement membrane proteins

Sequence motif analysis

Summary

  • Soft plaques are associated with lower level of ECM proteins
  • Soft plaques are associated with increased abundance of proteolytic enzymes
  • ECM proteins are subject to proteolytic degradation
  • ECM degradation is consistent with MMP activity

Thanks

  • Prof. Michael Davies
  • Prof. Henrik Sillesen, Prof. Jonas Eiberg, Karin Yeung
  • Christine Chuang
  • Protein Oxidation Group

Thank you for listening